Trial of Infusional FOLFIRINOX in First Line Treatment of Advanced Biliary Tract Cancers (FBI-TRAC)

January 13, 2024 updated by: Shouki Bazarbashi, King Faisal Specialist Hospital & Research Center

Phase II Trial of Infusional 5 FLUOROURACIL, LEUCOVORIN, OXALIPLATIN AND IRINOTECAN (FOLFIRINOX) in First Line Treatment of Advanced Biliary Tract Cancers

This study is to evaluate the response rate and toxicity profile of infusional 5 fluorouracil, leucovorin, oxaliplatin and irinotecan (FOLFIRINOX) in first-line treatment of advanced biliary tract cancers and also to assess progression free survival and overall survival of FOLFIRINOX in first line treatment of advanced biliary tract cancers

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Biliary tract carcinomas (BTCs) are invasive adenocarcinomas that arise from the epithelial cells of the biliary tree, which comprises intrahepatic and extrahepatic bile ducts, and the gallbladder. Even though BTCs are considered as rare tumors, they represent about 30% of the total primary liver cancers with an incidence rate close to that of hepatocellular carcinoma. Approximately 1200 new cases in the United Kingdom and 9000 in the United States are diagnosed annually. The Saudi Cancer Registry reported 911 case of gall bladder cancer, 318 intrahepatic cholangiocarcinoma and 574 extrahepatic cholangiocarcinoma between 1994 and 2009. Unfortunately, only a minority of patients diagnosed with these aggressive tumors present at an early resectable stage, and disease recurrence rates are high despite curative-intent surgery

The prognosis of patients with advanced biliary tract cancers is poor and median survival for those undergoing supportive care alone is short. Systemic chemotherapy is increasingly being applied in cases of advanced biliary tract cancers. A benefit for chemotherapy over best supportive care alone was suggested in a trial that randomly assigned 90 patients with advanced pancreatic or biliary cancer (37 with bile duct cancer) to fluorouracil (FU)-based systemic chemotherapy or best supportive care alone with median survival of 6 months for chemotherapy versus 2.5 months for best supportive care.

Different drugs has demonstrated activity in BTCs, including fluoropyrimidines, gemcitabine, cisplatin, and oxaliplatin. A pooled analysis from Eckel et al. that evaluated 104 trials with 2810 patients, has established gemcitabine combined with platinum compounds as the provisional standard of chemotherapy in advanced biliary tract cancer.

In a randomized phase two study of 51 patients, Kornek et al, established the efficacy of mitomycin in combination with gemcitabine or capecitabine in previously untreated patients with advanced biliary tract cancers. Mitomycin and capecitabine was associated with superior complete response rate (31% vs 20%), median progression free survival (5.3 months vs 4.2 months), and overall survival (9.25 months and 6.7 months). The EORTC 40955 trial randomized patients with BTCs to high dose 5FU vs combination of 5-FU, Leucovorin and cisplatin. The results showed that cisplatin and fluorouracil was more active than high-dose fluorouracil in terms of overall response rates (19% and 7.1%, respectively) and overall survival (8 months and 5 months, respectively), but progression free surviva; was similar in both treatment arms (3.3 months).

The randomized, controlled, phase three ABC-02 study, which enrolled 410 patients with locally advanced or metastatic cholangiocarcinoma, gallbladder cancer or ampullary cancer, demonstrated that the combination of gemcitabine and cisplatin improved overall and progression free survival by 30% over gemcitabine alone. Median overall survival was 11.7 months vs 8.1 months (HR, 0.64; 95% confidence interval, 0.52-0.80; p˂.001), and progression free survival was 8 months (HR, 0.51; 95% confidence interval, 0.51-0.77; p˂.001), both in favor of the combination arm. Although the rate of neutropenia was higher in the group receiving gemcitabine and cisplatin, there was no significant difference in the rate of neutropenia-associated infections between the 2 arms. Okusaka et al also reported similar findings in a phase two randomized study of 84 patients with advanced biliary tract cancers. Based on these results, the combination of gemcitabine and cisplatin is considered to be the standard of care for first-line chemotherapy for patients with advanced or metastatic biliary tract cancers.

Triple-drug chemotherapy regimens also have been shown to be effective in patients with advanced biliary tract cancers, albeit in a very small number of patients. The phase three trial that evaluated fluorouracil, leucovorin and etoposide versus fluorouracil cisplatin and epirubicin didn't show one regimen to be significantly superior with respect to overall survival (12 months vs. 9 months, respectively) in patients with advanced biliary tract cancers, although the trial was underpowered to detect such a difference.

In a phase two trial, the combination panitumumab, a monoclonal anti-epidermal growth factor receptor antibody, with gemcitabine and irinotecan showed encouraging efficacy with good tolerability in patients with advanced cholangiocarcinoma, with 5-month progression free survival rate of 69%.The median progression free survival and overall survival were 9.7 months and 12.9 months, respectively.

Results from the randomized phase three PRODIGE trial evaluating the combination of 5-Fluorouracil, Leucovorin, oxaliplatin and Irinotecan (FOLFIRINOX) versus gemcitabine alone in patients with metastatic pancreatic cancer and good performance status showed dramatic improvements in both median PFS (6.4 vs 3.3 months; P˂ .001) and median OS (11.1 months vs. 6.8 months; P˂ .001). Because of these strong results the National comprehensive cancer network (NCCN) and many other societies added FOLFIRINOX as a preferred, category 1 recommendation for first line treatment of good performance status patients with metastatic pancreatic cancer in 2011.

There are, however, some concerns about the toxicity of FOLFIRINOX regimen. In the PRODIGE trial, some of the grade 3 and 4 toxicity rates that were significantly greater in the FOLFIRINOX group than in the gemcitabine group were 45.7% for neutropenia, 12.7% for diarrhea, and 9.1 % for thrombocytopenia and 9% for sensory neuropathy.

Despite the high levels of toxicity, no toxic deaths have been reported. Furthermore, the PRODIGE trial determined that, despite this toxicity, fewer patients in the FOLFIRINOX group than in the gemcitabine group experienced a degradation in their quality of life at 6 months (31% vs. 66%,p ˂ .001). A more detailed analysis of the quality of life of patients in this trial has been published and shows that FOLFIRINOX maintained and even improved quality of life more than gemcitabine did.

Based on the above data, the investigators designed this phase two study of the efficacy and toxicity of FOFIRINOX regimen in first line treatment for patients with advanced biliary tract cancers. If the investigators achieved encouraging results, this regimen should then be compared with the standard combination of gemcitabine and cisplatin in future phase three trials.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
13

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Saudi Arabia
      • Riyadh, Saudi Arabia, 11211
        • King Faisal Specialist Hospital and Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Histologically confirmed locally advanced (irresectable) or metastatic biliary tract cancers.
  2. Measurable disease. Defined as tumor that have uni or bi dimensional measurement not less than 1.5 cm on any dimension.
  3. Age ≥ 18 years.
  4. Signed written informed consent before enrolment.
  5. No prior chemotherapy or anti-neoplastic therapy other than radiotherapy more than 4 weeks prior to enrolment and to areas other than the measurable disease.
  6. Patients of either sex or child bearing age must be willing to use adequate contraceptive measures during the study and for 6 months after treatment.
  7. Life expectancy of 6 months or more.
  8. Eastern Cooperative Oncology Group performance status of 0-1.
  9. Adequate renal function: creatinine within normal institutional range.
  10. Adequate hepatic function: Total bilirubin within normal institutional limits, serum aspartate aminotransferase and alanine aminotransferase levels ≤2.5 times the institutional upper limit of normal or ≤ 5 times the institutional upper limit of normal of elevated because of liver involvement.
  11. Adequate hematological values: leukocyte count ≥3.0 x 109/L, an absolute neutrophil count ≥1.5 x 109/L, a platelet count ≥100 x 109/L.

Exclusion Criteria:

  1. Known or suspected dihydropyrimidine deficiency.
  2. Presence of central nervous system metastasis.
  3. Previous malignancy within 5 years, except adequately treated non melanomatous skin cancer or in situ cervical cancer.
  4. Severe cardiovascular disease (congestive heart failure New York Heart Association class three or four, unstable angina pectoris, myocardial infarction or significant arrhythmias).
  5. Psychiatric or mental disorder, precluding understanding of the information of the trial related topics and giving valid informed consent.
  6. Active uncontrolled infection.
  7. Pregnant patients (confirmed by β-Human chorionic gonadotrophin test where appropriate).
  8. Serious underlying medical condition (in the judgement of the investigator) which could impair the ability of the patient to participate in the trial.
  9. Any psychological, familial, geographic or social circumstances which could impair the patient's ability to participate in the trial and comply with follow up.
  10. Treatment with other experimental drugs within 30 days of entry into the trial.
  11. Treatment with other anti-cancer therapy.
  12. Known hypersensitivity to any of the study drugs.
  13. Breast feeding
  14. Legal incapacity.
  15. Patients with a known diagnosis of HIV infection.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Experimental single arm

Chemotherapy using the FOLFIRINOX regimen will be given every 2 weeks for a total of 12 cycles. FOLFIRINOX consist of:

  1. Oxaliplatin-85 mg/m2 IV Day 1
  2. Leucovorin-400 mg/m2 IV Day 1
  3. Irinotecan-180 mg/m2 IV Day 1
  4. Fluorouracil (FU)-400 mg/m2 IV bolus Day 1
  5. Fluorouracil 2400 mg/m2 infused over 46 hours starting day 1
Combination product: FOLFIRINOX
combination chemotherapy using Oxaliplatin, Irinotecan, Leucovorin and Fluorouracil, given every 15 days for a total of 12 cycles

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Response rate
Time Frame: 3 year
Evaluate the response rate using RECIST 1.1 criteria
3 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
progression free survival
Time Frame: 4 years
calculated from day 1 of chemotherapy till either progression, death or date of last follow up whichever comes first
4 years
overall survival
Time Frame: 4 years
calculated from day 1 of chemotherapy till either death or date of last follow up whichever comes first
4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
King Faisal Specialist Hospital & Research Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Shouki Bazarbashi, King Faisal Specialist Hospital and Research cente

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 3, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 9, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 9, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 21, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 22, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 25, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 17, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 13, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RAC 2161 099

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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